What you carry at this position in your DNA and what research says about it.
Alzheimer Risk and ApoE Levels: 9/10 evidence, 12 publications.
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Sample genotype (not yours): A/A
Higher Risk of Alzheimer Disease
Promoter activity remains high, maintaining normal to elevated ApoE levels and increasing susceptibility to late-onset Alzheimer's.
What this genotype means: Increased risk of late-onset Alzheimer's disease; Standard to elevated ApoE protein expression.
Sample genotype (not yours): A/T
Reduced Risk of Alzheimer Disease
A single copy of the T allele slightly reduces ApoE promoter activity, offering moderate protection against Alzheimer's.
What this genotype means: Moderately lower risk of late-onset Alzheimer's; Slightly reduced ApoE promoter activity.
Sample genotype (not yours): T/T
Lowest Risk of Alzheimer Disease
Two copies of the T allele significantly lower ApoE promoter activity, providing strong protection against Alzheimer's.
What this genotype means: Significantly lower risk of late-onset Alzheimer's; Noticeably reduced ApoE promoter activity.
Gene function and biological role
Gene Function: The APOE gene encodes apolipoprotein E, a crucial protein involved in the transport and metabolism of cholesterol and other lipids throughout the body and brain. In the central nervous system, apolipoprotein E is primarily produced by astrocytes and plays a vital role in maintaining cellular membranes and repairing injured neurons [1]. It is also the most significant genetic determinant of late-onset Alzheimer's disease risk, largely due to how different protein isoforms interact with amyloid-beta plaques [2]. Beyond brain health, apolipoprotein E levels influence cardiovascular health by regulating circulating lipid levels and clearance [3].
Variant Impact: Located in the promoter region of the APOE gene, rs449647 is a regulatory variant that directly alters how much apolipoprotein E protein is produced. The substitution of an adenine (A) with a thymine (T) at this position reduces the transcriptional activity of the promoter, leading to lower levels of ApoE expression [1]. Because brain ApoE levels influence the clearance and accumulation of amyloid-beta, this regulatory change has a direct impact on susceptibility to neurodegenerative processes [2]. Research indicates that this promoter variant can modify cognitive decline and Alzheimer's risk independently of the well-known APOE epsilon-4 coding variant [4].
Key Insight: This promoter variant acts like a dimmer switch for the APOE gene, with the T allele reducing gene expression by up to 36 percent in brain cells.
Location: APOE. Chromosome 19 · 19q13.32 · 44.9 Mb
Estimated prevalence by population
Global 63.1%; European 68.2%; African 49.3%; East Asian 94.0%; South Asian 62.6%; Americas 60.2%; Ashkenazi 52.1%; Finnish 77.2%; Middle Eastern 40.0%; Amish 81.0%.
Estimated AA genotype frequency.
Global 32.1%; European 28.8%; African 41.8%; East Asian 5.9%; South Asian 33.0%; Americas 34.8%; Ashkenazi 40.2%; Finnish 21.3%; Middle Eastern 46.5%; Amish 18.0%.
Estimated AT genotype frequency.
Global 4.8%; European 3.0%; African 8.9%; East Asian 0.1%; South Asian 4.4%; Americas 5.0%; Ashkenazi 7.7%; Finnish 1.5%; Middle Eastern 13.5%; Amish 1.0%.
Estimated TT genotype frequency.
Showing effects for A/A genotype
Neurology & Mental Health
Neurodegenerative Diseases
Alzheimer's Disease. Evidence: 9/10. Source: PMID 21263195. ~1.5x Higher Risk.
Memory, Learning & Attention
Late-Life Memory. Evidence: 5/10. Source: PMID 37984853. Typical.
Cardiovascular & Metabolic
Lipids & Cholesterol
ApoE Protein Levels. Evidence: 4/10. Source: PMID 22028770. Normal Levels.
Showing effects for A/T genotype
Alzheimer's Disease. Evidence: 9/10. Source: PMID 21263195. Reduced Risk.
ApoE Protein Levels. Evidence: 4/10. Source: PMID 22028770. Possibly Lower.
Showing effects for T/T genotype
Alzheimer's Disease. Evidence: 9/10. Source: PMID 21263195. Lowest Risk.
ApoE Protein Levels. Evidence: 4/10. Source: PMID 22028770. Lower Levels.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Inheriting two copies of the A allele maintains standard promoter activity, resulting in typical or slightly elevated levels of apolipoprotein E in the brain [1]. While apolipoprotein E is necessary for lipid transport, higher expression driven by this genotype is consistently linked to an increased risk of developing late-onset Alzheimer's disease [2]. This elevated risk appears to operate independently of the classic APOE epsilon-4 status, suggesting that the sheer volume of ApoE protein produced plays a role in plaque dynamics [3]. Some studies also suggest that higher promoter activity may influence late-life memory performance and cognitive decline trajectories [4]. Maintaining a brain-healthy lifestyle with regular exercise and a balanced diet is highly recommended to mitigate these genetic risks.
Increased risk of late-onset Alzheimer's disease; Standard to elevated ApoE protein expression.
Sample genotype: AT (Heterozygous)
Possessing one copy of the T allele introduces a regulatory change that moderately dampens the transcription of the APOE gene [1]. This slight reduction in ApoE expression is associated with a lower risk of late-onset Alzheimer's disease compared to the common A/A genotype [2]. Because the risk of neurodegeneration is partially driven by the overall abundance of certain ApoE forms, a slight reduction in expression helps mitigate plaque-related pathology [3]. Cognitive studies in older cohorts suggest that this moderate reduction in promoter activity does not negatively impact general memory performance [4]. Overall, this genotype represents a favorable genetic buffer that supports long-term brain health.
Moderately lower risk of late-onset Alzheimer's; Slightly reduced ApoE promoter activity.
Sample genotype: TT (Homozygous)
Carrying two copies of the T allele significantly reduces the transcriptional activity of the APOE promoter, resulting in lower overall levels of apolipoprotein E in the brain [1]. This marked reduction in ApoE expression is strongly associated with a protective effect against late-onset Alzheimer's disease [2]. By limiting the total amount of ApoE protein available to interact with amyloid-beta, this genotype helps minimize the processes that lead to cognitive decline [3]. Despite the lower protein levels, overall lipid transport and late-life memory performance remain stable and typical [4]. This genetic profile is considered highly favorable for healthy brain aging and long-term cognitive preservation.
Significantly lower risk of late-onset Alzheimer's; Noticeably reduced ApoE promoter activity.
Variants with shared genetic architecture
rs429358 · APOE Gene · Chr 19 · Alzheimer's Disease Risk
rs7412 · APOE Gene · Chr 19 · Cholesterol and Heart Risk
rs769449 · APOE Gene · Chr 19 · Alzheimer's Disease Risk
Plasma proteome variation and its genetic determinants in children and adolescents.
Identification of 16 novel Alzheimer's disease loci using multi-ancestry meta-analyses.
Content updated August 2026.
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